PROJECT SUMMARY The overarching goal of the proposed research is to develop, pilot, and evaluate a linkage navigation program to enhance initiation and engagement in treatment for opioid use disorder (OUD) to prevent overdose. To date, empirical evidence to support strategies to identify and link individuals with OUD to treatment is sparse. One of the most promising strategies involves initiating patients identified in emergency department (ED) settings onto buprenorphine, then referring them for ongoing treatment in primary care. However, this intervention is dependent on patients exhibiting signs of moderate to severe opioid withdrawal when they present to the ED or discharging the patient with buprenorphine for self-induction. The intervention is also dependent on busy ED providers engaging in the process of induction and referral for ongoing treatment. In the initial trial, referral to treatment consisted of a 10 to 15 minute brief negotiation interview with a research associate. An alternative, and perhaps more sustainable, approach could be to apply the linkage to care models from HIV prevention to facilitate identification and linkage of individuals with OUD to treatment using an intervention that focuses on the referral to treatment component, irrespective of whether or not they are inducted onto buprenorphine in the ED. Given the 30% increase in ED visits for opioid overdose across the country in 2017, targeting interventions in the ED is essential. Our multidisciplinary team brings together years of experience in substance use research, emergency medicine, intervention development and evaluation, addiction medicine, patient navigation, and clinical care to address the following specific aims: 1) To develop an intervention to enhance linkage to initiation and engagement in treatment for individuals with opioid use disorder and 2) To assess acceptability, feasibility, and initial efficacy of an intervention to enhance linkage to initiation and retention in treatment for individuals with opioid use disorder plus clinician referral compared to clinician referral alone. Given the similarities between HIV and OUD, we will adapt the evidence-based Anti-Retroviral Treatment and Access to Services (ARTAS) protocol to enhance linkage of individuals with OUD to opioid agonist treatment. We will conduct a qualitative study that includes key informant interviews with persons who misuse opioids, treatment and clinical providers, and patient navigators to inform the essential modifications to ARTAS that would be necessary to enhance linkage to initiation and retention in treatment for OUD. Information from the interviews will be augmented with prior literature and other evidence-based models to finalize the pilot intervention. We will pilot the developed intervention in individuals with moderate to severe opioid use disorder who are not currently in treatment. We will recruit 108 participants from the Denver Health ED to compare the intervention (n=58) to standard of care (n=58) using a block randomization design. Our primary outcome will be treatment initiation within 30 days of randomization and secondary outcomes will include treatment engagement at one and three months, number of opioid use days, non-fatal overdose, and fatal overdose.